Department of Neurology, Jiangsu University Affiliated with Wujin Hospital (Wujin Clinical College of Xuzhou Medical University), Changzhou, China.
School of Basic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Kaohsiung J Med Sci. 2023 Oct;39(10):1002-1010. doi: 10.1002/kjm2.12745.
Butyrate (BU), a gut microbiota-derived metabolite, has been reported to play a neuroprotective role in Parkinson's disease (PD). However, the specific molecular mechanism of BU has not been fully interpreted. This work aimed to verify the protective effects of BU against MPTP/MPP -induced neurotoxicity and explore the mechanisms involved. The results showed that BU protected against MPTP-induced motor dysfunction and decreased tyrosine hydroxylase (TH) and dopamine transporter (DAT) levels. Additionally, BU pretreatment improved PC12 cell viability and reduced MPP -induced PC12 cell apoptosis. BU treatment also attenuated MPP -stimulated oxidative stress and inflammatory response in PC12 cells. Furthermore, BU inhibited MPTP/MPP -induced hyperactivation of the JAK2/STAT3 signaling in mice and PC12 cells. Besides, a JAK2 agonist, Coumermycin A1 (C-A1), substantially reversed BU-mediated inhibition on JAK2/STAT3 phosphorylation in MPP -challenged PC12 cells and abated BU-induced repression on MPP -triggered apoptosis, oxidative stress, and inflammatory response in PC12 cells. To sum up, BU might exert neuroprotective effects against MPP /MPTP-induced neurotoxicity by inactivating the JAK2/STAT3 signaling.
丁酸盐（BU）是一种肠道微生物衍生的代谢物，据报道在帕金森病（PD）中具有神经保护作用。然而，BU 的具体分子机制尚未完全解释。本工作旨在验证 BU 对 MPTP/MPP 诱导的神经毒性的保护作用，并探讨其涉及的机制。结果表明，BU 可预防 MPTP 诱导的运动功能障碍，并降低酪氨酸羟化酶（TH）和多巴胺转运体（DAT）水平。此外，BU 预处理可提高 PC12 细胞活力，减少 MPP 诱导的 PC12 细胞凋亡。BU 处理还可减轻 MPP 刺激的 PC12 细胞氧化应激和炎症反应。此外，BU 抑制了 MPTP/MPP 诱导的 JAK2/STAT3 信号在小鼠和 PC12 细胞中的过度激活。此外，JAK2 激动剂 Coumermycin A1（C-A1）可显著逆转 MPP 挑战的 PC12 细胞中 BU 介导的 JAK2/STAT3 磷酸化抑制，并减轻 BU 对 MPP 触发的 PC12 细胞凋亡、氧化应激和炎症反应的抑制作用。总之，BU 可能通过抑制 JAK2/STAT3 信号通路发挥对 MPP/MPTP 诱导的神经毒性的神经保护作用。
